Upregulation of oxidant-induced VEGF expression in cultured keratinocytes by a grape seed proanthocyanidin extract

Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the m ost prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. The wound site is rich in oxidants such as hydroge n peroxide mostly contributed by neutrophils and macrophages. Proanthocyani dins or condensed tannins are a group of biologically active polyphenolic b ioflavonoids that are synthesized by many plants. This study provides first evidence showing that natural extracts such as grape seed proanthocyanidin extract containing 5000 ppm resveratrol (GSPE) facilitates oxidant-induced VEGF expression in keratinocytes. Using a ribonuclease protection assay (R PA), the ability of GSPE to regulate oxidant-induced changes in several ang iogenesis-related genes were studied. While mRNA responses were studied usi ng RPA, VEGF protein release from cells to the culture medium was studied u sing ELISA. Pretreatment of HaCaT keratinocytes with GSPE upregulated both hydrogen peroxide as well as TNF-alpha -induced VEGF expression and release . The current results suggest that GSPE may have beneficial therapeutic eff ects in promoting dermal wound healing and other related skin disorders. (C ) 2001 Elsevier Science Inc.